5'‐ O ‐(2‐Isopropoxyprop‐2‐yl)‐protected Phosphoramidite Building Blocks in the Liquid Phase Oligonucleotide Synthesis

5'‐ O ‐(2‐isopropoxyprop‐2‐yl) (IIP)‐protection was introduced to 5’‐OH function of nucleosides in high yields by an acid‐catalysed transacetalization with 2,2‐diisopropoxypropane. The applicability of this temporal 5’‐ O ‐protecting group was demonstrated in the liquid phase oligonucleotide synthesis (LPOS) using the corresponding phosphoramidite building blocks (dA, dG, dC and dT) and a tetrapodal precipitative soluble support. Standard protecting groups were used on nucleobases. Tetrazole as an activator, followed by oxidation using m ‐chloroperbenzoic acid, was used for the coupling. The IIP was shown to be a capable choice to the 5’‐ O protection in solution phase synthesis. It could be readily removed with formic acid ( t 1/2